Clinical Case Study

By:Dr. Tikal Kansara

R3 Medicine D Unit

HISTORY OF CURRENT ILLNESS

• Fever for 3 days– High grade, with chills & rigors

• Vomiting for 3 days• Headache for 3 days– Severe, global, throbbing type

• Convulsions for 2 days– GTC type, total of 3 episodes

• Pain in left lower limb around hip for 2 days– After convulsions

PAST HISTORY

• Dimness of vision since age of 4 years– Progressive, improved after bilateral cataract surgery at

the age of 6 years• Recurrent episodes of convulsions since the age of

10 years– 1 – 2 episodes in a few months

• Headache since the age of 10 years – Intermittent episodes, each lasting a few hours to a day

or two– Frequency once in 15 to 20 days

• Generalized weakness & bodyache since the age of 10 years– Mild aches to begin with; progressed to an extent

that he was unable to cycle to school, so he left school

• Swelling on the outer side of right thigh 1 year ago– Painful, throbbing type– Relieved after Incision and Drainage– Left a 3 x 4 cm scar on right side of thigh

INTRAUTERINE HISTORY– No maternal history of any major medical illness during pregnancy. ANC and

Inj. TT regularly takenBIRTH HISTORY

– SFD – FTND. On some oral syrups for the sameDEVELOPMENTAL HISTORY

– All developmental milestones are not available but he started walking at 15 – 16 months age

– He was always the shortest in height in his schoolIMMUNISATION HISTORY

– All immunizations were takenFAMILY HISTORY

– Patient has no siblings– Cousin (maternal) is short statured

TREATMENT HISTORY– Had cataract surgery done at age of 6 years– Patient did not seek any medical attention for his convulsions

HISTORY CONCLUSIONSo, at the end of history of current illness, we have a 16 year old boy with acute onset of fever, vomiting, headache and convulsions with sequel of left lower limb pain; most likely we are dealing with a case of:• Acute Meningoencephalitis • Cerebral Malaria• Acute febrile illness reducing the seizure threshold

In a background of bilateral progressive cataracts, convulsions, generalised debilitating bodyache for nearly a quarter of decade, in a short stature child (s/o – failure to thrive) without auditory symptoms or symptoms of dyspnoea, squatting episodes or urinary disturbances (hematuria, polyuria, burning micturation); we are prompted to believe him as a part of syndrome, most likely being:• Hypoparathyroidism (eg. Familial, isolated)• Galactosemia (Classical)• Down Syndrome

• Hairs – Normal• Facial Features – Symmetrical• Teeth and Palate – Normal• Extremities – Normal• Palms and Soles – Normal• Pallor present

GENERAL EXAMINATION

MOTOR FUNCTIONS

• Nutrition:– Wasting present; but bilaterally symmetrical

• Tone:– Upper limb:

• Right: Reduced• Left: Reduced

– Lower limb:• Right: Reduced• Left: Not elicited

• Power– 4/5 in both upper limbs & right lower limb

REFLEX RIGHT LEFT

Biceps Jerk - -

Triceps Jerk - -

Supinator Jerk - -

Knee Jerk - -

Ankle Jerk - -

Ophthalmology Examiation

Pseudophakia with PCO (Posterior Capsular Opacity) present. Fundus not properly visualised.

Vision: FC 6 – 8 Feet on bedside. Further not possible

Stain: Negative

Tension:Right eye: 17.3 mmHg (Normal)Left Eye: 17.3 mmHg (Normal)

No abnormal eye movementsNormal ocular positionIntraocular pressure is normal

HISTORY & PE CONCLUSIONSo, at the end of history & PE, we have a 16 year old boy with acute onset of fever, vomiting, headache and convulsions with sequel of left lower limb pain; with tachypnea, tachycardia without signs of meningeal irritation;

In a background of bilateral progressive cataracts, convulsions, generalised debilitating bodyache for nearly a quarter of decade, in a short stature child (s/o – failure to thrive) without auditory symptoms or symptoms of dyspnoea, squatting episodes or urinary disturbances (hematuria, polyuria, burning micturation); with wasting, generalised hypotonia & areflexia we are prompted to believe him as a part of syndrome, most likely being:

• Hypoparathyroidism (Familial, isolated)• Galactosemia (Classical)• Fanconi Syndrome

INVESTIGATIONS

09 / 06 10 / 06 Normal ValuesHemoglobin 5.1 5.30 14 – 17 gm%Total WBC 7300 / cmm 5,800 / cmm 4000 – 11000 /cmmDifferentials 60 / 34 / 4 / 2 68 / 30 / 01 / 01Platelets 232000 Adequate 150000 – 45000 / cmmSmear Hypochromia + Mild Microcytic

Hypochromic RBCsFew Elliptocytes

Malarial Parasite Not detected Not detected

ESR 40

09 / 06 10 / 06 Normal ValuesUrea 113 mg/dl 115 mg/dl 14 – 40 mg/dlCreatinine 12.6 mg/dl 14.16 mg/dl M: 0.7 – 1.4 mg/dlBilirubin (T) 0.6 mg/dl 0.1 – 0.2 mg/dlBilirubin (D) 0.2 mg/dl 0 – 0.4 mg/dlBilirubin (ID) 0.4 mg/dl 0.1 – 0.8 mg/dl

BIOCHEMICAL INVESTIGATION

09 / 06 10 / 06 12 / 06 Normal ValuesS. Na 134 135 – 145 mEq/LS. K 3.2 2.7 3.5 – 5.5 mEq/LS. Calcium (T) 8.7 7.9 8.4 – 10.3 mg/dlS. Calcium (I) 0.9 1.1 – 1.35 mmol/LS. Phosphorus 5.5 2.6 – 4.5 mg/dlS. Magnesium 2.6 M: 1.8 – 2.6 mg/dlS. Chloride 114 98 – 107 mmol/L

SERUM ELECTROLYTES

URINE REPORT (11 / 06 / 2016)

Color Yellow

Appearance Slightly turbid

Reaction (pH) 6.0

Specific Gravity 1.020

Chemical Examination

Urine Albumin Present (++)

Urine Sugar (Qualitative) Present (+)

Ketones Absent

Microscopic Examination

Pus cells / hpf 2 – 3 / hpf

RBC / hpf 2 – 5 / hpf

Epithelial cells / hpf Occassional / hpf

Casts / lpf Absent

Crystals Absent

Yeast / Fungus Absent

Widal Test (08 / 06)

S. Typhi “O” 1 : 120

S. Typhi “H” 1 : 60

10 / 06 Normal Values

S. Protein 7.2 6.0 – 8.0 gm/dl

S. Albumin 3.4 3.2 – 5.0 gm/dl

S. Globulin 3.8

ECG Normal

RBS 122 mg / dL

TSH 0.62 (Normal Range: 0.27 – 4.20 µIU/ml)

Viral Markers

HIV Negative

HbsAg Negative

HCV Negative

Liver:Size: NormalEchopattern: NormalNo dilated IHBR/Focal lesionPV at porta: Normal CBD: Normal

Pancreas: Size: Normal; Normal echopattern, no focal lesion

Spleen: Size 8.9 cm normal. Normal echopattern, no focal lesionRight Kidney:

Size 6.6 x 2.1 cmShows mild hydronephrosisNo e/o calculus noted

Left Kidney:Size: 5.4 x 2.2 cmNo e/o calculus/hydronephrosis noted

Bilateral kidneys appear small in size with loss of cortico-medullary differenciation

IMPRESSION:Changes of chronic renal parenchymal disease

ULTRASOUND ABDOMEN

CEREBROSPINAL FLUID EXAMINATIONCEREBROSPINAL FLUID EXAMINATIONPhysical Examination

Amount 1 mlColour ColourlessAppearance Slightly turbidBlood Absent

Biochemical ExaminationProtein 120 mg/dlSugar 96 mg/dlADA level 0.39 U/L

Microscopic ExaminationTotal Count 70 cells/mlTotal RBCs Rare cells/mlDifferential 75 / 25

Microscopic ExaminationGram & Zn stain No organism detected

MRI BRAIN – PLAIN + CONTRAST

• No significant diagnostic intracranial abnormality detected

X-Rays• X-Ray PBH:– Reduced bone density

noted involving visualized bones with # neck left femur with upward displacement of shaft of left femur

– Bilateral hip joint space appears preserved

• X-Ray B/L knee (AP & Lateral):– Reduced density of

visualized bones noted with dense sclerosis of the metaphysis of the bones (Tibia & Fibula)

– B/L knee joint space is preserved

• CXR - PA

13 / 06 14 / 06pH 7.30 7.15P CO2 20.6 mmHg 26.0 mmHgP O2 64 mmHg 52 mmHgOxygen Saturation 90.6 % 76.8 %cHCO3 9.9 mmol/L 8.6 mmol/L

ARTERIAL BLOOD GAS ANALYSIS

Hospital Course

09 / 06 10 / 06 11 / 06 12 / 06 13 / 06 14 / 06 14 / 06

Creatinine 12.6 14.16 9.03 5.46 3.65 3.49 3.79

HD 1 HD 2 HD 3

13 / 06 14 / 06

pH 7.30 7.15

P CO2 20.6 mmHg 26.0 mmHg

P O2 64 mmHg 52 mmHg

Oxygen Saturation 90.6 % 76.8 %

cHCO3 9.9 mmol/L 8.6 mmol/L

Underlying metabolic acidosis

Bicarbonate supplementation added to prescription

Interpretation of Investigations

• Anion Gap = (Na + K) – (Cl + HCO3) = (134 + 3.2) – (114 + 9.9)

= 13.3 (Normal)• Hypokalemia

• Hyperchloremia• Metabolic acidosis worsened in spite of HCO3 supplementation

09 / 06 10 / 06 12 / 06 13 / 06 15 / 06S. K 3.2 2.7 3.4 3.3

13 / 06 14 / 06pH 7.30 7.15cHCO3 9.9 mmol/L 8.6 mmol/L

• So, we have a hyperchoremic metabolic acidosis with hypokalemia, without evidence of renal stones (No symptoms & USG not s/o stones), which worsens in spite of bicarbonate supplementation

• These features are s/o Type II (Proximal) Renal Tubular Acidosis

TYPE 1 DISTAL RTA TYPE 2 PROXIMAL RTA TYPE 4 RTA

DefectReduced H+ excretion in distal tubule

Impaired HCO3 reabsorption in proximal tubule

Impaired cation exchange in distal tubule

Hyperchloremic Normal anion gap metabolic acidosis

Yes Yes Yes

Minimum urine pH

> 5.5 (always) < 5.5 (ill – defined) < 5.5

Plasma HCO3 < 15 Usually >15 Usually > 15

Plasma K Low-normal Low-normal High (always)Renal Stones Almost always present No No

Causes

Hereditary - Band 3 mutation (association with sensorineural deafness)

Aquired – Autoimmune (eg Sjogren), cirrhosis, sickle cell anaemia, renal transplantation

Hereditary – Cystinosis, Wilson dz, galactosemia, fructose intolerance, etc

Aquired – Amyloidosis, Multiple Myeloma, Paroxysmal Nocturnal Hemoglobinuria, HAART

Disorders of renal interstitum and tubules with GFR > 20 mL/min

• In addition to this, the patient has features of reduced bone mineral density on X-Rays (Osteomalacia >> Renal Osteodystrophy)– With pathological # following convulsions (a trivial

trauma)• Proteinuria• Glucosuria• Failure to thrive & anaemia

• So, combining the two ,we have– Hyperchloremic– Metabolic acidosis– Hypokalemia– Radiological features of reduced bone density severe

enoughfor pathological # of long bone (left femur) (s/o long standing loss of calcium & phosphorus in urine)

– Proteinuria– Glucosuria– Failure to thrive

• These features comprise - Fanconi Syndrome

Favours Fanconi Syndrome in our patient Against Fanconi Syndrome in our patient

Metabolic Acidosis <<None>>

Hypokalemia <<None>>

Hyperchloremia <<None>>

Proteinuria (Mild) as no edema in the patient during the last decade & normal serum albumin

<<None>>

Glucosuria <<None>>

Failure to thrive <<None>>

After advanced medicorenal disease sets in, amino acids may not be found in urine. But wasting was present, s/o reduced muscle mass

Did not perform urinary loss of amino acids

Already an advanced medicorenal disease with shrunken kidney has set in.Features on X-Ray & anthropometry are have features of chronically reduced phosphorus & calcium

Hyperphosphatemia

Did not demonstrate phosphaturia

Fanconi Syndrome

• Inherited –– Cystinosis, Wilson disease, Lowe Syndrome,

Galactosemia, Glycogen storage disease, Hereditary Fructose Intolerance

• Aquired – – Outdated Tetracyclines, Tenofovir & didanosine,

Multiple Myeloma and monoclonal gammopathy

Combining everything available !!!• Fanconi Syndrome• Bilateral cataracts (operated); with resurrgence of

posterior capsular opacity• Long history of convulsions (without any structural

lesions in brain) & hypotonia with areflexia on examination

Oculo Cerebro RenalSyndrome

LOWE SYNDROME

Lowe Syndrome

• X-linked recessive syndrome• Incidence 1:200,000 to 1:500,000• Congenital cataracts, hypotonia and areflexia,

proximal tubular acidosis, aminoaciduria, phosphaturia and low molecular weight proteinuria with intellectual disability

• Diagnosed by inositol polyphosphate 5-phosphatase enzyme activity in cultured skin fibroblasts and by OCRL1 gene study